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The effect of phomopsins on selenium metabolism in sheep

Beetson, Susan Annette (1994) The effect of phomopsins on selenium metabolism in sheep. PhD thesis, Murdoch University.

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Lupinosis is a mycotoxicosis caused by the ingestion of phomopsin toxins produced by the fungus Phomopsis leptostromiformis Kuhn (Bubak) which colonises lupin plants. Lupinosis is recognised primarily as an hepatic disease of sheep, however it is also associated with the occurrence of a myopathy. The myopathy is termed lupinosis associated myopathy (LAM) and is histologically indistinguishable from vitamin E/selenium responsive nutritional myopathy. Despite repeated attempts by others, LAM is nonresponsive to conventional selenium and vitamin E therapy. The main aim of this work was to investigate the relationship between LAM, selenium and vitamin E.

In order to correctly assess and stage the hepatic pathology associated with exposure to phomopsins, the biochemical indicators of hepatocellular damage and hepatic function were examined. BSP clearance, plasma bilirubin concentration, plasma AST activity and feed intake were the best indicators of concurrent hepatic pathology of individual sheep exposed to phomopsins. BSP clearance, bile acids and plasma bilirubin concentration provided the most accurate indication of the concurrent hepatic status of flocks of sheep grazing lupin stubble. Although plasma AST activity was previously thought to be an adequate indicator of the degree of active hepatocellular damage in a flock, its usefulness was dependent on the duration and the degree of intoxication.

The effect of lupinosis on selenium metabolism in sheep was examined. Phomopsin A intoxication significantly affected the storage and metabolism of selenium in sheep. This was a specific effect of phomopsins. Exposure to phomopsins significantly altered the whole blood and plasma pharmacokinetics, tissue distribution and excretion patterns of 75 Se-selenite and 75 Se-selenomethionine when given orally or intravenously. Furthermore these alterations affected the liver's capacity to produce selenoproteins, thereby changing the supply and metabolism of the body's selenium pool. Consequently the profound change in selenium metabolism resulted in muscle pathology. In contrast to this, the bioavailability of selenium from an intramuscular dose of either 75 Se-selenomethionine and 75 Se-selenite was unaffected by exposure to phomopsin toxin. This work was the first to monitor and relate alterations in selenium kinetics and metabolism to a specific pathological process.

A field trial was carried out to determine the effectiveness of intramuscular selenite and selenomethionine with and without vitamin E supplementation in preventing LAM. Pre-treatment of sheep with both selenomethionine and vitamin E prior to exposure to toxic lupin stubble significantly reduced the incidence of LAM. This was the first effective treatment of LAM. Selenite and vitamin E supplementation, either alone or in combination was not effective. Selenomethionine supplementation alone was also unsuccessful. The apparent necessity for both selenomethionine and vitamin E indicates that there is a significant metabolic and functional interaction between the two nutrients during the pathogenesis of LAM.

Item Type: Thesis (PhD)
Murdoch Affiliation(s): School of Veterinary Studies
Supervisor(s): Costa, Nick
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